The regulatory volume increase response results in the rapid uptake of NaCl and a number of organic osmolytes. To increase cell volume there is an activation of the Na+-H+ antiporter (NHE-1), the 1Na+,1K+,2Cl− symporter (NKCC1), and a number of cation-selective channels, which together bring NaCl into the cell. The Na+,K+-ATPase then extrudes the Na+ in exchange for K+ , so that ultimately the KCl content of the cell is increased. Several organic osmolyte transporters are also activated to increase cell volume. These include a 3Na+,1Cl−-taurine symporter, a 3Na+,2Cl−-betaine symporter, a 2Na+–myo-inositol symporter, and a Na+– amino acid symporter. These transporters use the energy in the Na+ and Cl− gradients to drive the secondary active uptake of these organic osmolytes into cells.
The regulatory volume decrease response results in the loss of KCl and organic osmolytes from the cell. The loss of KCl occurs through the activation of a wide range of K+selective, Cl−-selective, and anion-selective channels (the specific channels involved vary depending on the cell), as well as through activation of K+-Cl− symporters. Some of the organic osmolytes appear to leave the cell via anion channels (e.g., volume-sensitive organic osmolyte-anion channels).
Several mechanisms are involved in activation of these various transporters during the volume regulatory
CHAPTER 2 Homeostasis: Volume and Composition of Body Fluid Compartments 2Cl Na+, Cl– Na+ + •Fig. 2.7 Volume Regulation of Cells in Hypotonic and Hypertonic Media. Top, Whencellsareexposedtoahypotonicmedium,theyswellandthenundergoavolume-regulatorydecrease(RVD).TheRVDinvolveslossofKClandorganicosmolytesfromthecell.ThedecreaseincellularKClandorganicosmolytescausesintracellularosmoticpressuretodecrease,waterleavesthecell,andthecellreturnstonearlyitsoriginalvolume.Bottom, Whencellsareexposedtoahypertonicmedium,theyshrinkandthenundergoavolume-regulatoryincrease(RVI).DuringtheRVI,NaClandorganicosmolytesenterthecell.TheincreaseintheactivityofNa+,K+-ATPase(notdepicted)enhancestheexchangeNa+ forK+ sothattheK+ (andCl−)contentofthecellisincreased.TheincreaseincellularKCl,alongwithariseinintracellularorganicosmolytes,increasesintracellularosmoticpressure,whichbringswaterbackintothecell,andthecellvolumereturnstonearlyitsoriginalvolume.π,theoncoticpressureinsidethecell.
responses. Changes in cell volume appear to monitored by the cytoskeleton, by changes in macromolecular crowding and ionic strength of the cytoplasm, and by channels whose gating is influenced, either directly or indirectly, by stretch of the plasma membrane (e.g., stretch-activated cation channels). A number of second messenger systems may also be involved in these responses (e.g., intracellular [Ca++], calmodulin, protein kinase A, and protein kinase C), but the precise mechanisms have not been defined completely.
Principles of Epithelial Transport